Lovastatin Alters TGF-β-Induced Epithelial-Mesenchymal Transition in Porcine Lens Epithelial Cells

被引:12
作者
Urakami, Chikako [1 ]
Kurosaka, Daijiro [1 ]
Tamada, Kunifusa [1 ]
Kishimoto, Seishi [2 ]
Tezuka, Yu [3 ]
Nishigori, Hideo [3 ]
机构
[1] Iwate Med Univ, Dept Ophthalmol, Sch Med, Morioka, Iwate 0208505, Japan
[2] Teikyo Univ, Fac Pharmaceut Sci, Tokyo 173, Japan
[3] Iwate Med Univ, Dept Pharmacotherapeut, Sch Pharm, Yahaba, Iwate, Japan
关键词
Lens epithelial cells; epithelial-mesenchymal transition; TGF-beta; statin; gel contraction; GROWTH-FACTOR-BETA; SMOOTH MUSCLE ACTIN; ANTERIOR CAPSULE CONTRACTION; CYTOSKELETAL REORGANIZATION; CATARACT-SURGERY; KINASE PATHWAY; RHO; EXPRESSION; TRANSDIFFERENTIATION; FIBROSIS;
D O I
10.3109/02713683.2012.665121
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
Purpose: To determine whether lovastatin affects the epithelial-mesenchymal transition (EMT) in porcine lens epithelial cells (LECs) induced by transforming growth factor-beta (TGF-beta). Materials and Methods: Porcine LECs were cultured in Dulbecco's Modified Eagle Medium (DMEM) for 24 h. The cultured cells were then exposed or not exposed to lovastatin (10 mu M) for 18 h and then stimulated with or not stimulated with TGF-beta 2 (5 ng/ml) for 24 h. The expression of alpha-smooth muscle actin (alpha-SMA), a marker of myofibroblasts, was determined by real-time PCR, and the expression of alpha-SMA protein was determined by Western blot. The effect of lovastatin on the expression of the mRNA of collagen type 1 (COL1) was determined by real-time PCR. To assess cell contractility, LECs were cultured in collagen gel with or without pretreatment of lovastatin and exposure of TGF-beta 2. The longest and shortest diameters of the gels were measured and the area was determined. Results: Exposure of LECs to TGF-beta 2 increased the expression of the mRNA and protein of alpha-SMA and the mRNA of COL1A1. TGF-beta 2 increased the degree of contraction of collagen gel. These findings indicated that TGF-beta 2 promoted EMT, and the pretreatment of the LECs with lovastatin blocked these changes induced by TGF-beta 2. Conclusion: Lovastatin inhibits the TGF-beta-induced EMT of cultured porcine LECs. This suggests that lovastatin should be considered as a new agent to prevent postoperative complications associated with EMT of LECs.
引用
收藏
页码:479 / 485
页数:7
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